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Antibiotic therapy in musculoskeletal infection
- 1. ANTIBIOTIC THERAPY IN MUSCULOSKELETAL INFECTION Presenter: Dr. Namith R JR Orhtopaedics Moderator: Prof Vijay Kumar Co-moderator: Dr. Manoj
- 2. Learning objectives • Musculoskeletal infection • Antibiotic recommendation • Periprosthetic infections • Prophylactic antibiotic therapy • Common antibiotics
- 3. Musculoskeletal infections • Soft tissue infections • Osteomyelitis • Joint infection/ Septic arthritis • Prosthetic joint infection
- 4. Selection of Antibiotic • Type of infection • Culture / Sensitivity • Hospital sensitivity patterns, • Risk vs benefit
- 5. Routes • Oral - most commonly used. • Intravenous - serious infections • Local delivery
- 6. Soft Tissue Infection • Most common- staph areus, staph epidermidis, strep pyogenes • MRSA has increased incidence
- 7. Drug Doses GRAM POSITIVE • Frist choice- Neficillin 2g 6hrly or Clindamycin 900mg 8hrly • Alternate – Vancomycin 500mg 8hrly or Cephalothin • MRSA- Vancomycin 500mg TID or Neficillin • Group A and B Staph: Penicillin G 2* 4hrly • 2nd choice- Clindamycin or Cephalothin • Enterococcus- Ampicillin 2gm 6hrly • 2nd choice Vancomycin
- 8. Gram Negative Frist choice- • Tobramycin 5mg/kg 8thhrly • Ampicillin 2gm 6hrly • Cefotaxime 2gm 8hrly • Cefazolin 2gm 8hrly • Ticarcillin 3gm 4hrly • Gentamycin 5mg/kg 8th hrly
- 9. Osteomyelitis • Infection of the bone • Types- Acute or Chronic • Haematogenic or Exogenous • Pyogenic or Granulomatous
- 10. Location • Tubular bones with most rapid growth and largest metaphyses are most commonly affected, 75% • Femur > tibia > fibula; distal end > proximal end • Flat bones are less frequently infected, 25% • Neonates : metaphysis and/or epiphysis • Children : metaphysis • Adults : epiphyses and subchondral regions
- 11. MC isolated organism • <1 yr- Group B streptococcus, • <1 yr- Group B streptococcus, Staph.aureus, E.coli Staph.aureus, E.coli • 1 to 16 yr- Staph.aureus, Strep.pyogenes • >16yr- Staph.aureus, Strep.epidermidis • >16yr- Staph.aureus, Strep.epidermidis, Pseudomonas, E.coli, Serratiamarcescens
- 12. Treatment • Flucloxacilin and ampicilin started iv • Continue until blood c/s report • Antibiotic for 6weeks • Monitor ESR
- 13. PMMAAntibiotic Bead Chains • Local concentrations of antibiotic achieved are 200 times higher • Aminoglycosides - most commonly employed antibiotics for use with PMMA beads • Currently, most commercially available bone cements have a prepackaged form available with gentamicin (500 mg/40g pack). • We generally add 2 to 4 g of vancomycin, with or without 1 g of tobramycin, to each 40g pack before adding the monomer
- 15. Septic Arthritis • S. aureus is most frequently isolated • N. gonorrhoeae is more common in adults younger than 30 years • H. influenzae type B is more common in children younger than 2 years.
- 16. • Trial of antibiotic treatment is appropriate only after culture material has been obtained. • If the patient does not respond to antibiotic treatment in 36 to 48 hours, the wrong antibiotic has been chosen or an abscess has formed • After 48 hours, specific antibiotic can be chosen • If an abscess has formed, surgery is indicated.
- 17. Periprosthetic Infection Definition: • There is a sinus tract communicating with the prosthesis; or • A pathogen is isolated by culture from at least two separate tissue or fluid samples obtained from the affected prosthetic joint; or
- 18. Four of the following six criteria exist: • Elevated (ESR) and (CRP) , • (b) Elevated synovial leukocyte count, • (c) Elevated synovial PMN%, • (d) Presence of purulence in the affected joint, • (e) Isolation of a microorganism in one culture of periprosthetic tissue or fluid, or • (f) Greater than five neutrophils per high-power field in five high-power fields
- 21. Microorganism Preferred Treatmenta Alternative Treatmenta Staphylococci, oxacillin- susceptible Nafcillinb sodium 1.5–2 g IV q4-6 h Vancomycin IV 15 mg/kg q12 h or or Cefazolin 1–2 g IV q8 h Daptomycin 6 mg/kg IV q 24 h or or Ceftriaxonec 1–2 g IV q24 h Linezolid 600 mg PO/IV every 12 h Staphylococci, oxacillin- resistant Vancomycind IV 15 mg/kg q12 h Daptomycin 6 mg/kg IV q24 horLinezolid 600 mg PO/IV q12 h Enterococcus spp, penicillin-susceptible Penicillin G 20–24 million units IV q24 h continuously or in 6 divided doses or Ampicillin sodium 12 g IV q24 h continuously or in 6 divided doses Vancomycin 15 mg/kg IV q12 h or Daptomycin 6 mg/kg IV q24 h or Linezolid 600 mg PO or IV q12 h Enterococcus spp, penicillin-resistant Vancomycin 15 mg/kg IV q12 h Linezolid 600 mg PO or IV q12 h or Daptomycin 6 mg IV q24 h Pseudomonas aeruginosa Cefepime 2 g IV q12 h Ciprofloxacin 750 mg PO bid or or 400 mg IV q12 h Meropeneme 1 g IV q8 h or Ceftazidime 2 g IV q8 h
- 22. Prophylactic Antibiotic Therapy • During the first 24 hours, infection depends on the number of bacteria present • During the first 2 hours, the host defense mechanism works to decrease the overall number of bacteria • During the next 4 hours, the number of bacteria remains fairly constant • These first 6 hours are called the “golden period,” after which the bacteria multiply exponentially
- 23. • Begin immediately before surgery (ideally 30 minutes before skin incision). • A maximal dose of antibiotic should be given and can be repeated every 4 hours intraoperatively or whenever the blood loss exceeds 1000 to 1500 mL. • Little is gained by extending antibiotic coverage over 24 hours. • m/c used is 2nd generation cephalosporins. • β-lactams such as cephalosporins, penicillin and its derivatives such as cloxacillin, glycopeptides - teicoplanin and aminoglycosides - gentamicin.
- 25. Cefuroxime • Second-generation cephalosporin • susceptible to beta-lactamase • greater activity against Staph Areus, Haemophilus influenzae, Neisseria gonorrhoeae • Side effect: diarrhea, nausea, vomiting, headaches/migraines, dizziness, and abdominal pain
- 26. Vancomycin • Glycopeptide antibiotic • Surgical prophylaxis/treatment for major procedures involving implantation of prostheses in institutions with a high rate of MRSA or MRSE • MIC S. aureus: 0.25 μg/ml to 4.0 μg/ml S. aureus (methicillin resistant or MRSA): 1 μg/ml to 138 μg/ml S. epidermidis: ≤0.12 μg/ml to 6.25 μg/ml
- 27. • SIDE EFFECT: Anaphylaxis Toxic epidermal necrolysis Erythema multiforme Red man syndrome Thrombocytopenia Neutropenia Ototoxic Nephrotoxic
- 28. Teicoplanin • Glycopeptide antibiotic • Spectrum similar to vancomycin – Gram +ve Bac • MIC: Staphylococcus aureus: ≤0.06 μg/ml - ≥128 μg/ml Staphylococcus epidermidis: ≤0.06 μg/ml - 32 μg/ml
- 29. System organ classCommon (≥1/100 to <1/10 ) Uncommon (≥1/1,000 to <1/100) Rare (≥1/10,000 to <1/1,000) Infections and infestations Abscess Blood and the lymphatic system disorders Leucopenia, thrombocytopenia, eosinophilia Immune system disorders Anaphylactic reaction (anaphylaxis) Nervous system disorders Dizziness, headache Ear and Labyrinth disorders Deafness, hearing, tinnitus, vestibular disorder Vascular disorders Phlebitis Respiratory, thoracic and mediastinal disorders Bronchospasm Gastro-intestinal disorders Diarrhoea, vomiting, nausea Skin and subcutaneous tissue disorders Rash, erythema, pruritus Red man syndrome (e.g. Flushing of the upper part of the body) Renal and Urinary disorders Blood creatinine increased
- 30. Gentamicin • Aminoglycoside • Irreversibly binding the 30S subunit • Wide range- mostly Gram-negative bacteria • Dose: 3mg/kg with normal renal functions
- 31. • Side effects: • Most nephrotoxic of the class • Ototoxic • Low blood counts • Allergic responses • Neuromuscular problems • Nerve damage
- 32. Linezolid • Oxazolidinone class • Protein synthesis inhibitor • Resistant gram positive bacteria • 600 mg IV or orally every 12 hours
- 33. Side effect: • Severe diarrhea or diarrhea that is watery or bloody • Fungal infections • Thrombocytopenia • Myelosuppression • Serotonin syndrome • Nerve problems • Angioedema • Fever, chills, body aches, flu symptoms
- 34. Rifampicin • Ansamycins class • DNA-dependent RNA polymerase inhibitor • MIC: Mycobacterium tuberculosis : 0.002 – 64 µg/mL Stapylococcus aureus (methicillin resistant) :≤0.006– 256 µg/mL
- 35. Side effects: • Liver toxicity — hepatitis, liver failure in severe cases • Respiratory — breathlessness • Cutaneous — flushing, pruritus, rash, hyperpigmentation, redness and watering of eyes • Abdominal — nausea, vomiting, abdominal cramps, diarrhea • Flu-like symptoms — chills, fever, headache
- 36. THANK YOU
Editor's Notes
- Musculoskeletal infections are classified according to the affected structures in:
- Alternate • Mezlocilin, Imipenem, amikacin,Mezlocilin,, Ceforoxime, Ceftazidime• Anaerobic-• Clindamycin 900mg • Pencillin G 2 X 10Pencillin G 2 X 4hrly • Alternate- Metronidazole, Cefoxitine
- Penicillins, cephalosporins, and clindamycin are eluted well from PMMA beads; vancomycin elutes much less effectively Antibiotics such as the fluoroquinolones, tetracycline, and polymyxin B are broken down during the exothermic process of cement hardening and should not be used with PMMA beads
- Whiteside et al. described a one-stage débridement and revision with a cementless prosthesis and intraarticular infusion of vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) infections. After débridement and implantation of the prosthesis, patients received two 1-g doses of vancomycin intravenously over 24 hours, and then only intraarticular infusion of vancomycin, keeping blood levels between 3 and 10 µg/mL. Seventeen of 18 documented MRSA infections were successfully treated using this technique, as was one recurrent infection.
- Parvizi, Javad & Zmistowski, Benjamin & Berbari, Elie & W Bauer, Thomas & Springer, Bryan & J Della Valle, Craig & L Garvin, Kevin & Mont, Michael & Wongworawat, Montri & G Zalavras, Charalampos. (2011). New Definition for Periprosthetic Joint Infection: From the Workgroup of the Musculoskeletal Infection Society. Clinical orthopaedics and related research. 469. 2992-4. 10.1007/s11999-011-2102-9.
- Enterobacter spp Cefepime 2 g IV q12 h or Ertapenem 1 g IV q24 h Ciprofloxacin 750 mg PO or 400 mg IV q12 h Enterobacteriaceae IV β-lactam based on in vitro susceptibilities or Ciprofloxacin 750 mg PO bid β-hemolytic streptococci Penicillin G 20–24 million units IV q24 h continuously or in 6 divided doses or Ceftriaxone 2 g IV q24 h Vancomycin 15 mg/kg IV q12 h Propionibacterium acnes Penicillin G 20 million units IV q24 h continuously or in 6 divided doses or Ceftriaxone 2 g IV q24 h Clindamycin 600–900 mg IV q8 h or clindamycin 300–450 mg PO qid or Vancomycin 15 mg/kg IV q12 h
- During the first 24 hours, infection depends on the number of bacteria present. During the first 2 hours, the host defense mechanism works to decrease the overall number of bacteria. During the next 4 hours, the number of bacteria remains fairly constant, with the bacteria that are multiplying and the bacteria that are being killed by the host defenses being about equal. These first 6 hours are called the “golden period,” after which the bacteria multiply exponentially. Antibiotics decrease bacterial growth geometrically and delay the reproduction of the bacteria. The administration of prophylactic antibiotics expands the golden period.
- Namias et al. found that antibiotic coverage for longer than 4 days led to increased bacteremia and intravenous line infections in patients in intensive care units. Evidence now shows that 24 hours of antibiotic administration is just as beneficial as 48 to 72 hours. cefazolin was the most used antibiotic in preoperative prophylaxis, combination of cefazolin with gentamicin was the second common regimen while 3rd generation cephalosporin were 3rd widely used antibiotics.2 National clinical practice guidelines on rationale use of antibiotics in orthopedic surgery in Malaysia recommends cloxacillin in combination with gentamicin as first choice, 2nd generation cephalosporin as second choice antibiotics in arthroplasty and open reduction and internal fixation of fracture The trend in western literature is to use 2nd generation cephalosporins (cefuroxime) prophylactic antibiotics 30 min to 1 h before skin incision and preferable for 24 h to 3 days in intravenous infusion postoperatively Cefuroxime has high bioavailability in tissue and serum after a single dose and is efficacious for preventing perioperative infection.
- Early in treatment as an empiric antibiotic for possible MRSA infection while waiting for culture identification of the infecting organism
- ncluding Pseudomonas, Proteus, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Serratia, and the Gram-positive Staphylococcus.[9]
- Enterococcus faecium and Enterococcus faecalis (including vancomycin-resistant enterococci), Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus, MRSA), Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, the viridans group streptococci, Listeria monocytogenes, and Corynebacterium